Tapentadol Eases OA Pain

Action Points

Explain to interested patients that tapentadol, a pain reliever with both mu-opioid receptor agonism and norepinephrine reuptake inhibition, was superior to placebo in relief of knee osteoarthritis pain and was associated with fewer side effects than oxycodone.

Note that the study was limited by a small sample size and a restricted patient population.

The centrally acting, extended-release analgesic tapentadol provided effective pain relief in patients with knee osteoarthritis, but with fewer of the gastrointestinal side effects seen with oxycodone, a phase III study found.

Tapentadol significantly reduced average pain intensity from baseline to week 12 compared with placebo, with a least squares mean difference of −0.7 (95% CI −1.04 to −0.33), according to Marc Afilalo, MD, of Sir Mortimer B. Davis Jewish General Hospital in Montreal, and colleagues.

The incidence of constipation -- a particular problem with opioids -- was significantly lower in the tapentadol group than in the oxycodone group (18.9% versus 36.8%, P<0.001), the researchers reported in the August issue of Clinical Drug Investigation.

Tapentadol has two mechanisms of action, in that it exhibits mu-opioid receptor agonism and norepinephrine reuptake inhibition, which is thought to enhance the opioid analgesic effects.

To see if an extended release formulation of the drug would be a safe, effective option for patients with knee osteoarthritis, Afilalo and colleagues recruited 1,023 patients from 87 sites in North America, Australia, and New Zealand, randomizing them to twice-daily oral doses of tapentadol 100 mg to 250 mg, twice-daily controlled release oxycodone in doses of 20 mg to 50 mg, or placebo.

Patients' mean age was 58 years, the majority were women, and more than 80% rated their baseline pain as severe.

The study included a three-week titration period, which was followed by a 12-week maintenance phase.

Pain intensity was significantly reduced for the tapentadol group not only at week 12 but also for the overall maintenance period, with a least squares mean difference of −0.7 (95% CI −1 to −0.33).

In contrast, the average pain intensity with oxycodone was significantly reduced for the overall maintenance period compared with placebo (−0.3, 95% CI −0.67 to 0), but not at week 12 (−0.3, 95% CI −0.68 to 0.02).

The percentage of patients achieving a 50% or greater reduction in average pain intensity at week 12 was significantly higher in the tapentadol group compared with placebo (32% versus 24.3%, P=0.027).

In the oxycodone group, however, the percentage reaching that level of pain reduction at week 12 was lower than in the placebo group (17.3% versus 24.3%, P=0.023).

Among patients in the tapentadol, oxycodone, and placebo groups, 20.2%, 13.5%, and 8.4%, respectively, reported that their overall status was "very much improved" at the end of treatment, while 38.4%, 33.5%, and 27.1% said they were "much improved."

"Treatment with tapentadol ER 100 mg to 250 mg was associated with a clinically significant decrease in pain intensity compared with placebo," the investigators wrote.

The overall incidence of adverse events was 75.9% with tapentadol, 87.4% with oxycodone, and 61.1% with placebo, with the most common events being nausea, constipation, vomiting, somnolence, headache, and dizziness.

Along with constipation, nausea and/or vomiting was significantly lower in the tapentadol group than in the oxycodone group (22.7% versus 40.6% P<0.001).

Adverse events led to study withdrawal in 19.2% of the tapentadol group, 42.7% of the oxycodone group, and 6.5% of the placebo group.

The addition of norepinephrine reuptake inhibition to opioid receptor agonism may produce an opioid-sparing effect that is responsible for the higher degree of tolerability seen with tapentadol, the investigators explained.

Limitations of the study include its sample size and restricted patient population.

Further studies should help to more fully establish the adverse effect profile of the drug and to determine the association between tolerability and adherence, they concluded.

The study was funded by Johnson & Johnson Pharmaceutical Research & Development.

The lead author received funding for study support from Johnson & Johnson, but declared that he had no other conflicts of interest.

The co-authors are employees and shareholders in Johnson & Johnson or employees of Grünenthal.

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